Diagnostic and clinical significance of antigen-specific pancreatic antibodies in inflammatory bowel diseases: A meta-analysis

Table 2 Characteristics of the included studies evaluating the diagnostic accuracy of glycoprotein 2 antibodies in Crohn’s disease

Ref.	Country	Multicenter	Recruitment			CD diagnosis and classification		Assays characteristics					Sample characteristics					Funding
			Year	Site	Consecutive	CD diagnosis	Montreal[81]	Assay	Kit	anti-GP2 form	Blind assay	Positivity cut-off U/dL	N9	Unrelated sample	Children included	Sex (% female)	Age (yr)5
Bogdanos et al[41]	Germany; United Kingdom	√	NR	Otto-von-Guericke University; UCL Hospital; and Children’s hospital Technical University Dresden	NR	Standard clinical, radiological, endoscopical and histological criteria[8,9]	√	ELISA	GA (Dahlewitz/Berlin Germany)	Total	No	IgA 20; IgG 20	CD n = 169; UC n = 102; HC n = 225	NR	√	CD 60.3%; UC 55.9%	CD 36 (8-87)1; UC 47 (17-92)1	Higher Education Funding Council of England; Biomedical Research Centre, United Kingdom NIHR; and Brandenburg Ministry of Economics; and EU
Bonaci-Nikolic et al[42]	Serbia	NR	NR	Clinical Center of Serbia	NR	Clinical, endoscopic, histologic, lab findings[21]	-	ELISA	GA (Dahlewitz/Berlin Germany)	Total	No	IgA 20; IgG 24	CD n = 33; UC n = 23; GSE n = 21; HC n = 13	NR	-	CD 42.4%; UC 56.5%; GSE 76.2%; HC 46.1%	CD 35 (19-63)4; UC 34 (24-57)4; GSE 31 (19-57)4; HC 41 (22-55)	None declared
Caneparo et al[43]	Italy	-	2008-2014	Policlinico San Donato	NR	Clinical, endoscopic and histologi-cal criteria	-	ELISA	GA (Dahlewitz/Berlin Germany)	Total	√	IgA 10; IgG 15	CD n=48 UC n=26 HC n=182	NR	√	CD 47.9%; UC 19.2%	CD 41 (16-65)4; UC 39 (17-62)4	Regione Piemonte and Letizia Castelli Schubert Foundation
Cummings et al[44]	United Kingdom	-	2009 -2010	Cleveland Clinic	√	Clinical, endoscopic, radiographic, histopathological criteria[22]	-	ELISA	GA (Dahlewitz/Berlin Germany)	Isoforms GP21 and GP24	√	IgA GP21 14; IgA GP24 3.7; IgG GP21 18; IgG GP24 15	UC n = 117	√	-	UC 44.4%	UC 44.3 ± 13.7	Obtained but not disclosed
Degenhardt et al[45]	Germany	-	2000-2006	University Medical Center Regensburg	NR	European Crohn and Colitis Organization criteria[23]	√	ELISA	GA (Dahlewitz/Berlin Germany)	Isoform alpha and betta	√		CD n =303; UC n =108; OGD n = 72; OPC n = 206	NR	√	CD 52.8%; UC 39.8%; ODG 36.1%	CD 36.1 ± 12.5; UC 40.2 ± 12.8; OGD 60.3 ± 13.8	Bundesministerium für Bildung & Forschung and Kompetenznetz chronisch entzündliche Darmerkrankungen
Gross et al[46]	Netherlands	NR	NR	VU University Medical Center Amsterdam	-	Lennard-Jones criteria[24]	-	ELISA	GA (Dahlewitz/Berlin Germany)	Total	No	IgA 20; IgG 20	CD n = 38; UC n = 40; CeD n = 45; GFD n = 34; RCD n = 15	NR	-	CD 71.1%; UC 52.5%	CD 36.4 ± 11.8; UC 36.5 ± 9.6	CD consortium
Michaels et al[47]	Germany	-	2005-2013	University Hospital Schleswig-Holstein	-	Typical clinical, endoscopical, histological and/or radiological findings of CD/UC	√	IIF	Euroimmun Germany	Total	NR		CD n = 224; UC n = 136	NR	NR	CD 64.3%; UC 54.4%	CD 392; UC 422	Else-Kröner-Fresenius-Stiftung
Op De Beéck et al[48]	Belgium	-	NR	University Hospital Gasthuisberg, Leuven	NR	Lennard-Jones criteria[24]	-	ELISA	GA (Dahlewitz/Berlin Germany)	Total	NR	IgA 15; IgG 15	CD n = 164; UC n = 118; OGD n = 75	NR	√	CD 58.6%6; UC 41.7%6[59]; ODG NR	CD 42 (17-80)16; UC 43 (19-78)1,6[59]; ODG NR	Fund for Scientific Research Flanders and GA GmbH
Papp et al[49]	Hungary	-	2005-2010	Institute of Internal Medicine, University of Debrecen	√	Lennard-Jones criteria[24]	√	ELISA	GA (Dahlewitz/Berlin Germany)	Total	√	IgA 20; IgG 20	CD n = 271; UC n = 187; HC n = 100	NR	-	CD 61.5%; UC 54%	CD 25 (19-33); UC 33 (23-43)	Janos Bolyai Research Scholarship; Debrecen University; and IOIBD Research
Pavlidis et al[50]	United Kingdom	-	NR	UCL Hospital	NR	Lennard-Jones criteria[24]	√	ELISA	GA (Dahlewitz/Berlin Germany)	Total	NR	IgG 20	CD n = 225; UC n = 225	NR	-	CD 56.4%; UC 49.7%	CD 36 ± 14.3; UC 51 ± 15.7	NIHR; Higher Education Funding Council for England; EASL; and INOVA Diagnostics
Pavlidis et al[51]	United Kingdom	-	NR	UCL Hospital	√	Lennard-Jones criteria[24]	√	ELISA	Inova Diagnostics (Research use only)	Total	√	IgA 20; IgG 25	CD n = 323; UC n = 294; OPC n = 112; HC n = 103	NR	-	CD 54%; UC 47.9%	CD 40 ± 14.3; UC 48.7 ± 15.7	INOVA Diagnostics
Pavlidis et al[52]	United Kingdom	-	NR	UCL Hospital	NR	Lennard-Jones criteria[24]	√	IIF	N/A8	Total	NR		CD n = 212; UC n = 249	NR	-	CD 42.4%; UC 51.4%	CD 42.4 (30-49); UC 51.4 (37-61)	Euroimmun
Röber et al[53]	Germany	√	1994-2014	Three children’ s University hospitals (Dresden, Leipzig, Giessen)	NR	Porto criteria[25]	Paris [82]	ELISA	GP21, GP23: (AMS Biotechnology, Abingdon, United Kingdom); GP22: (CCS GmbH, Hamburg, Germany); GP24: (Thermo Sci, Braunschweig, Germany)	Isoforms 1, 2, 3, 4	NR	IgA GP21 7.02; IgA GP22 7.33; IgA GP23 4.37; IgA GP24 9.01; IgG GP21 33.38; IgG GP22 71.75; IgG GP23 15.89; IgG GP24 23.22	CD n = 164; UC n = 114; GE n = 27; ENDO n =56; HC n =218	NR	√	CD 39.6%; UC 54.3%; GE 52%; ENDO 50%	CD 13 (10-15); UC 14 (11-15); GE 2 (1-5); ENDO 13 (7-16)	None declared
Roggenbuck et al[56]	Germany; Greece; Belgium	√	NR	Attikon Hospital, UoA; Otto-von-Guericke University; and University Hospital Leuven	NR	NR. Communication with an author, confirmed the Lennard-Jones criteria[24]	-	ELISA	GA (Dahlewitz/Berlin Germany)	Total	NR		CD n = 73; CeD n = 79; HC n = 90	NR	√7	CD 52%; CeD 69.6%	CD 36.5 (30-43)3; CeD 24 (12-42)3	None declared
Roggenbuck et al[55]	Germany	-	NR	Charité Berlin	NR	Lennard-Jones criteria[24]	-	ELISA	GA (Dahlewitz/Berlin Germany)	Total	NR	IgA 20; IgG 20	CD n = 73; UC n = 49; HC n = 63	NR	-	CD 57.5%; UC 59.1%	CD 41 (20-72)1; UC 40 (21-71)1	Brandenburg Ministry of Economics and EU
Roggenbuck et al[54]	Germany	NR	NR	NR	√	Lennard-Jones criteria[24]	NR	ELISA	GA (Dahlewitz/Berlin Germany)	Total	NR	IgA 20; IgG 20	CD n = 178; UC n = 100; HC n = 162	NR	-	CD 60.7%; UC 54%	CD 39 (18-87)1; UC 42 (18-71)1	Brandenburg Ministry of Economics and EU
Zhang et al[57]	China	-	NR	Peking Union Medical College Hospital	NR	Lennard-Jones criteria[24]	√	ELISA	GA (Dahlewitz/Berlin Germany)	Total	NR	IgA 20; IgG 20	CD n = 35; UC n = 35; OGD n = 13; HC n = 8	NR	√	CD 17%; UC 38%; ODG NR	CD: 17 (13-69)1; UC: 38 (18-75)1; ODG NR	NNSFC
Zhang et al[58]	China	-	NR	Peking Union Medical College Hospital	√	Lennard-Jones criteria[24]	√	ELISA	GA (Dahlewitz/Berlin Germany)	Total	NR	IgA 10; IgG 15	CD n = 171; UC n = 208; BD n = 71; ITB n = 57; HC n = 70	NR	√	CD 33%; UC 43%; BD 38%; ITB 43%	CD 33 (10-85)1; UC 43 (12-77)1; BD 38 (10-73)1; ITB 43 (14-76)1	NNSFC; Chinese Academy of Medical Sciences; and Chinese Key Research & Development Program

¹Median (minimum-maximum).

²median.

³Mean (IQR1-IQR3).

⁴Mean (minimum-maximum).

⁵mean ± standard deviation, or median, IQR.

⁶Not all participants from the Joossens[59] study were included.

⁷Not among participants with Crohn’s disease.

⁸Using as substrates IIF chip slides containing sections of unfixed pancreas, recombinantly transformed HEK293 cells-overexpressing GP2[83].

⁹Healthy controls were not included in the sensitivity and specificity analyses herein. Anti-GP2: Glycoprotein 2 antibodies; BD: Behçet's disease; CD: Crohn’s disease; CeD: Celiac Disease; EASL: European association for the study of liver; ENDO: Nonspecific gastrointestinal symptoms; ELISA: Enzyme-linked immunosorbent assay; EU: European Union; GA: Generic assays; GE: Acute gastroenteritis; GFD: CeD on gluten-free diet; GP2: Glycoprotein 2; GSE: Gluten-sensitive enteropathy; HC: Healthy controls; IBD: Inflammatory bowel diseases; IIF: Indirect immune-fluorescence; ITB: Intestinal tuberculosis; N/A: Not applicable; NIHR: National Institute for Health Research; NNSFC: National Natural Science Foundation of China; NR: Not reported; OGD: Other gastrointestinal disease; OPC: Other pathological conditions; RCD: Refractory Crohn’s disease; UC: Ulcerative Colitis; UCL: University College London; UoA: University of Athens.